Department of Physiology, College of Medical Science, China Three Gorges University, 8 University Road, 443002, Yichang, Hubei, People's Republic of China.
J Mol Neurosci. 2014 Sep;54(1):49-58. doi: 10.1007/s12031-014-0246-2. Epub 2014 Feb 9.
Inflammation plays a pivotal role in the pathogenesis of many diseases in the central nervous system. Caudate nucleus (CN), the largest nucleus in the brain, is also implicated in many neurological disorders. 2-Arachidonoylglycerol (2-AG), the most abundant endogenous cannabinoid and the true natural ligand for CB1 receptors, has been shown to exhibit neuroprotective effects through its anti-inflammatory action from proinflammatory stimuli in hippocampus. However, it is still not clear whether 2-AG is also able to protect CN neurons from proinflammation stimuli. In the present study, we discovered that 2-AG significantly protects CN neurons in culture against lipopolysaccharide (LPS)-induced inflammatory response. 2-AG is capable of suppressing elevation of LPS-induced cyclooxygenase-2 expression associated with ERK/p38MAPK/NF-κB signaling pathway in CB1 receptor-dependant manner in primary cultured CN neurons. Moreover, 2-AG inhibits LPS-induced increase in voltage-gated sodium channel currents and hyperpolarizing shift of activation curves through CB1 receptor-dependant pathway. Our study suggests the therapeutic potential of 2-AG for the treatment of some inflammation-induced neurological disorders and pain.
炎症在中枢神经系统的许多疾病的发病机制中起着关键作用。尾状核（CN）是大脑中最大的核，也与许多神经疾病有关。2-花生四烯酸甘油（2-AG）是最丰富的内源性大麻素，也是 CB1 受体的真正天然配体，已被证明具有神经保护作用，可通过其抗炎作用来抵抗海马体中的促炎刺激。然而，目前尚不清楚 2-AG 是否也能够保护 CN 神经元免受促炎刺激。在本研究中，我们发现 2-AG 可显著保护培养的 CN 神经元免受脂多糖（LPS）诱导的炎症反应。2-AG 能够抑制 LPS 诱导的环氧合酶-2 表达的升高，这与 CB1 受体依赖性的 ERK/p38MAPK/NF-κB 信号通路有关，在原代培养的 CN 神经元中。此外，2-AG 通过 CB1 受体依赖性途径抑制 LPS 诱导的电压门控钠通道电流增加和激活曲线的超极化偏移。我们的研究表明 2-AG 具有治疗某些炎症引起的神经疾病和疼痛的潜力。
